1. Switch to LPV/r monotherapy
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Switch to LPV/r monotherapy
Pilot LPV/r
M03-613
LPV/r Mono
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OK04
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MOST
HIV-NAT 077 1

2. M03-613 Study: Switch to LPV/r monotherapy
Design
Randomisation
2 : 1
Open-label
W96 *
N = 104
LPV/r 400/100 mg bid
+ ZDV/3TC
LPV/r 400/100 mg bid
monotherapy
HIV+, ARV-naïve
HIV-1 RNA > 1000 c/mL
Any CD4 cell count
No documented resistance
N = 51
EFV 600 mg QD + ZDV/3TC
* Patients with HIV-1 RNA < 50 c/mL on 3 consecutive measures between W24 and W48 discontinued ZDV/3TC and remained on LPV/r monotherapy
Endpoints
Primary: proportion of patients with HIV-1 RNA < 50 c/mL at W96 (ITT-exposed, previous-failure = failure analysis) ; 80% power to detect a difference of 25% in response rate
Secondary: lipoatrophy (> 20% loss in limb fat) at W96 ; 70% power to detect a 20% difference in the mean change in limb fat percentage
M03-613
Cameron DW, JID 2008;198:234-40

3. M03-613 Study: Switch to LPV/r monotherapy
Baseline characteristics and patient disposition
79% of patients were male
65% were white
Mean age was 38 years
Mean baseline HIV-1 RNA was 4.9 log10 c/mL
Patients in the LPV/r group had a higher mean baseline HIV-1 RNA and a higher mean age
112 patients (57% in the LPV/r group and 69% in the EFV group) completed their assigned treatment regimen out to week 96
In the LPV/r group, after a median of 24 weeks, 92 patients (88%) simplified to LPV/r monotherapy
M03-613
Cameron DW, JID 2008;198:234-40

4. M03-613 Study: Switch to LPV/r monotherapy
ARV-trial.com
M Study: Switch to LPV/r monotherapy
Outcome at week 96
ITT-E
Non completion = failure analysis*
EFV +
ZDV/3TC
LPV/r mono
Confirmed HIV-1 RNA < 50 c/mL after 72 weeks post-simplification
91%
57%
(Kaplan-Meier estimate,
p < 0.001)
Confirmed virologic rebound (HIV-1 RNA > 500 c/mL) -
N = 12
4/7 achieved HIV-1 RNA < 50 c/mL after NRTI intensification
Mean change in CD4/mm3 at W96
+ 240
+ 289
(p = 0.12)
Development of resistance
to EFV,
N = 1
to PI, N = 4
(3 on LPV/r mono*, 1 on LPV/r + ZDV+3TC*) 63 60 % 20 40 80
100
95% CI for the
difference =
- 29% ; 4% 61 48
- 19% ; 13%
HIV-1 RNA
< 50 c/mL
* Confirmed virologic failure before W96 and
reintensified therapy with NRTIs were ignored
* major PI mutations in all 4 cases
EFV
LPV/r mono
M03-613
Cameron DW, JID 2008;198:234-40

5. M03-613 Study: Switch to LPV/r monotherapy
HIV-1 RNA level and discontinuation status, by visit, through 96 weeks % 20 40 60 80
100 16 32 48 64 96
Weeks % 20 40 60 80
100 16 32 48 64 96
Weeks
LPV/r
EFV
HIV-1 RNA > 500 copies/mL
HIV-1 RNA copies/mL
HIV-1 RNA < 50 copies/mL
Discontinued LPV/r or EFV
M03-613
Cameron DW, JID 2008;198:234-40

6. M03-613 Study: Switch to LPV/r monotherapy
Median percent change from baseline in limb fat and trunk fat
Scatter plot of percent change from baseline to W96 in limb fat vs trunk fat
-30
-20
-10 10 20 30 24 48 72 96
EFV limb fat
LPV/r trunk fat
EFV trunk fat
LPV/r limb fat
Weeks *
* p < 0.001
-50
-25 25 50 75
100
-40 40 80
120
Lipoatrophy
(p < 0.001)
Lipohypertrophy
LPV/r (N = 74)
EFV (N = 32)
% change in limb fat at week 96
% change in trunk fat at week 96
M03-613
Cameron DW, JID 2008;198:234-40

7. M03-613 Study: Switch to LPV/r monotherapy
Adverse events
Most common (frequency > 5%) moderate or severe adverse events related to treatment
LPV/r monotherapy group
Diarhoea: 15%
Nausea: 14%
EFV group
Asthenia: 12%
Dizziness: 12%
Insomnia: 12%
Rash: 10%
Depression: 6%
Most frequent grade 3 or 4 laboratory abnormalities
Total cholesterol > 7.8 mmol/L: 12% ; Triglycerides > 8.5 mmol/L: 7%
Amylase > 2 ULN: 6%
Amylase > 5 ULN: 10%
ALAT > 5 ULN: 6%
M03-613
Cameron DW, JID 2008;198:234-40

8. M03-613 Study: Switch to LPV/r monotherapy
Conclusions
LPV/r monotherapy was less effective than EFV + ZDV/3TC in maintaining virologic suppression: time to confirmed virologic rebound was shorter with LPV/r monotherapy
Lipoatrophy was significantly lower in the LPV/r monotherapy group
M03-613
Cameron DW, JID 2008;198:234-40